Familial Hypercholesterolaemia — Signs, Diagnosis, and Treatment (2026)
- FH affects 1 in 250 people — approximately 300,000 in the UK — most undiagnosed
- People with untreated FH have a 20× higher risk of premature heart disease
- FH cannot be controlled with diet alone — medication is essential from an early age
- PCSK9 inhibitors reduce LDL by 50–60% on top of maximum statin therapy
- Cascade screening — testing all first-degree relatives — is the most effective detection method
What Is Familial Hypercholesterolaemia?
Familial hypercholesterolaemia (FH) is a genetic condition causing persistently very high LDL cholesterol from birth. It is caused by mutations in the LDL receptor gene (or related genes), preventing normal LDL clearance from the blood. Unlike diet-related high cholesterol, FH cannot be adequately controlled through lifestyle alone — medication is essential.
Signs of Familial Hypercholesterolaemia
- Very high LDL cholesterol: Typically above 4.9 mmol/L (190 mg/dL) — often above 6–8 mmol/L in untreated FH
- Xanthomas: Cholesterol deposits in tendons — typically Achilles tendon or hand tendons (feeling like nodules)
- Xanthelasma: Yellow cholesterol deposits around the eyelids
- Corneal arcus: Grey-white ring around the cornea (before age 45 suggests FH)
- Family history: Parent, sibling, or child with very high cholesterol or premature heart disease (under 60 in men, under 65 in women)
How FH Is Diagnosed
In the UK, the Simon Broome criteria are used for diagnosis:
- Definite FH: Total cholesterol above 7.5 mmol/L (adults) + tendon xanthomas, OR LDL above 4.9 + genetic mutation identified
- Possible FH: Total cholesterol above 7.5 + family history of premature heart disease or high cholesterol
Treatment
High-Intensity Statin (Always Required)
Rosuvastatin 20–40mg or atorvastatin 40–80mg — typically started as early as possible (including childhood). Reduces LDL by 40–50%.
Ezetimibe (Usually Added)
Added to statin — reduces LDL by additional 18–20%. Available as Ezetrol or combined with atorvastatin as Liptruzet.
PCSK9 Inhibitors (Specialist Prescribing)
Evolocumab (Repatha) or alirocumab (Praluent) — injectable monthly or fortnightly. Reduce LDL by additional 50–60% on top of statin + ezetimibe. NHS-approved for FH patients who cannot reach target LDL. Now available as 6-monthly injection (inclisiran).